In the continuing search for novel substances from marine invertebrates originally distributed in Taiwan waters. The octocoral Briareum excavatum was transplanted to the culturing tanks located in the NMMBA for its interesting chemical constituents. This study had led to the isolation of 32 briarane derivatives 1¡V32, including 18 new compounds, briaexcavatins I¡VZ (1¡V18) from the cultured B. excavatum. The structures of compounds 1¡V32 were determined by spectroscopic methods and the structures of briaexcavatins I (1), U (13), W (15) and the known compound excavatolides C (19) and E (20) were confirmed by X-ray data analysis. The absolute configurations of briaranes 13 and 20 were determined by X-ray diffraction analysis and modified Mosher¡¦s method, respectively. It is noteworthy to mention that briaexcavatin Y (17) represents the first example of a briarane possessing a C-8/9 epoxy group. The relationships between 13C NMR chemical shifts and the conformations of the briaranes possessing an 11,12-epoxy group are described. In biological activity experiments, briaranes 11, 19, and 24 exhibited weak cytotoxicity toward CCRF-CEM tumor cells and compounds 2 and 19 showed weak cytotoxicity toward DLD-1 tumor cells, respectively. Moreover some of these briaranes such as compounds 24, 26, and 27 have displayed mild inhibitory effects on superoxide anion generation by human neutrophils. Compounds 14, 24, 26, and 30 showed mild inhibitory effects on human neutrophil elastase release. Compound 18 exhibited mild activity to enhance human neutrophil elastase release.

In connection with our long-standing interest in the chemical constituents of Formosan octocorals, we have investigated the octocorals Briarium excavatum and Junceella fragilis, collected at southern Taiwan coast. During the investigation, four new metabolites brianthiens D‐G (1‐4), have been isolated from Briareum excavatum. In addition, four 11,20-epoxybriaranes including three new metabolites, fragilides B‐D (5‐7), along with a known briarane (¡V)-11£\,20£\-epoxy-4-deacetoxyjunceellolide D (8), have been obtained from J. fragilis. The structure of 8 was revised as (¡V)-11£],20£]-epoxy-4-deacetoxyjunceellolide D (8) by detailed spectral data analysis. The structures, including the relative configurations of the new briaranes 1‐7, were elucidated by spectroscopic methods. The structure of fragilide B (5) was further confirmed by X-ray diffraction analysis. The relationship between 13C NMR chemical shifts and conformation of the cyclohexane ring in briaranes possessing 11,20-epoxy group, are also described.

In order to search for bioactive compounds, we have studied the chemical constituents from the organic extracts of one soft corals Klyxum simplex and two gorgonians Subergorgia mollis and Briareum excavatum. This study had led to the isolation of twenty-seven natural compounds 1¡V27, including nineteen new eunicellin¡Vtype diterpenoids, simplexins A¡VS (1¡V19) from K. simplex, one new steroid 11£\,15£\-diacetoxy-17£]-pregna-4,20- dien-3-one (20) along with one known compound 17£]-pregna-4,20-dien-3- one (21) from S. mollis, and six new briarane¡Vtype diterpenoids briaexcavatolides Q (22), S¡VV (23-26) and W (27) from B. excavatum. The structure of these compounds were established by the detailed spectroscopic analysis (IR, MS, 1D¡B2D NMR) and by comparison of the physical and spectral data with those of the related known compounds. The absolute configuration of 1 was determined by using a modified Mosher's method. The cytotoxicity of compounds 1¡V6, 9, 13¡V15 against the MCF-7 (human breast adenocarcinoma), Hep2 (human laryngeal carcinoma), Daoy (human medulloblastoma), and Hela (human cervical epitheloid carcinoma) cancer cell lines were determined. Compounds 1, 4 and 14 showed weak inhibition against the growth of MCF-7, Hep2 and Daoy, but did not inhibit the growth of Hela cells. Compound 5 exhibited a weak cytotoxicity against the growth of MCF-7, Hep2, Hela and Daoy cells. In addition, the activity of compounds 1¡V6, 9, 13¡V15 to inhibit the pro-inflammatory iNOS and COX-2 protein expression in LPS-stimulated RAW264.7 macrophage cells was estimated. Compound 5 showed the best anti-inflammatory activity among the all tested compounds.

This dissertation mainly presented the investigation of natural products from two different Formosan gongonian soft corals, Briareum violacea and Junceella fragilis. Their extracts were examined by intensive chromatographic methods. Eighty-four compounds including fifty new briaranes were isolated, and parts of their biological activities were studied. Natural products investigation of the Taiwanese gorgonian octocoral Junceella fragilis found fifteen new briarane-type diterpenes, namely frajunolides E-S (1-15), ninteen known briaranes, eg. junceellin, junceellolides A-E¡Bjunceellolide K, 11£\,20£\-epoxy-4-deacetoxyjuncellolide D, umbraculolide A, junceellonoid A, juncin P, juncins Y-ZI, frajunolides A-D and praelolide, and a sterol, ergosterol peroxide. Soft coral B. violacea (Quoy and Gaimard) of Taiwan has isolated thirty-five new briarane-type diterpenoids, briaviolides A-Z (16-41) and viobrianolides A-I (42-50), in addition to fourteen known diterpene lactones, stylatulide lactone, excavatolide A, 9-deacetylstylatulide lactone, 4£]-acetoxy-9-deacetylstylatulide lactone¡B Brianthein Z¡B, renillafoulin A, braexcavatolide E, braexcavatolide I, minabein-4, minabein-6, milolide K, solenolide A, and solenolides D-E. Structures of all above compounds were examined by physical and spectroscopic analyses including mass, IR, UV spectra, optical rotation and 1D, 2D NMR, as well as in comparison with the published data. Moreover, the structures of compounds 16, 32 and prarlolide were further confirmed by single X-ray crystallographic analysis. The stereochemistry of these compounds was investigated by NOESY method, and the configuration of compounds 32-38 were determined by Circular Dichroism spectroscopic analysis. Cytotoixcity and in vitro anti-inflammatory activities were studied by Dr. Kuo, Yao-Haur and Dr. Hwang, Tsong-Long, respectively. Junceellin, junceellolide B and juncin ZI exhibited weak cytotoxicity against Hep2 (Human laryngeal carcinoma), Doay (Human medulloblastoma), WiDr (Human colon adenocarcinoma), Hela (Human cervical epitheloid carcinoma). The in vitro anti-inflammatory activities of 1-7 were evaluated for inhibition of elastase release and for the generation of superoxide anion, as tested on human neutrophils. Compounds 1 and 6 exhibited weak inhibition of elastase release and superoxide anion at 10 £gg/mL. The biological activity analysis of compounds 16-50 are in progress.

Soft corals of the genus Briareum (Briareidae) have been well known as a rich source for marine natural products with novel structural features. Briarane-related natural products attracted the attentions of researchers because of the structural complexity and interesting biological activity associated with numerous compounds of this type. Previous studies on the secondary metabolites of wild-type and cultured Formosan octocoral Briareum excavatum were collected around the sea area of Kenting. In the thesis of our studies on secondary metabolites from marine organisms, the acetone-soluble of the Formosan octocoral B. excavatum collected at Orchid Island has led to the isolation of eleven briarane-type diterpenoids (1−11), compounds 3, 4, and 6−10 are new compounds. The structures of these compounds were determined on the basis of their spectroscopic analysis (1H NMR, 13C NMR, 1H−1H COSY, HSQC, HMBC, NOESY, IR and mass spectra) and physical data by comparison of the physical and spectral data with those of the related literatures. The antiviral activity against HCMV (human cytomegalovirus) cells of these secondary metabolites was evaluated. Metabolite 8 exhibited significant activity against HCMV cells and compound 11 showed anti-inflammatory activity.−